DOCSLIB.ORG

Versatile Naphthalimide Tetrazines for Fluorogenic Bioorthogonal Labelling† Cite This: DOI: 10.1039/D1cb00128k Ab Ab Cd E Marcus E

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Versatile Naphthalimide Tetrazines for Fluorogenic Bioorthogonal Labelling† Cite This: DOI: 10.1039/D1cb00128k Ab Ab Cd E Marcus E RSC Chemical Biology View Article Online PAPER View Journal Versatile naphthalimide tetrazines for fluorogenic bioorthogonal labelling† Cite this: DOI: 10.1039/d1cb00128k ab ab cd e Marcus E. Graziotto, Liam D. Adair, Amandeep Kaur, Pauline Ve´rite´, Sarah R. Ball,c Margaret Sunde, cd Denis Jacquemin e and Elizabeth J. New *abd Fluorescent probes for biological imaging have revealed much about the functions of biomolecules in health and disease. Fluorogenic probes, which are fluorescent only upon a bioorthogonal reaction with a specific partner, are particularly advantageous as they ensure that fluorescent signals observed in biological imaging arise solely from the intended target. In this work, we report the first series of naphthalimide tetrazines for bioorthogonal fluorogenic labelling. We establish that all of these compounds can be used for imaging through photophysical, analytical and biological studies. The best candidate was Np6mTz, where the tetrazine ring is appended to the naphthalimide at its 6-position via a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. phenyl linker in a meta configuration. Taking our synthetic scaffold, we generated two targeted variants, LysoNpTz and MitoNpTz, which successfully localized within the lysosomes and mitochondria Received 10th June 2021, respectively, without the requirement of genetic modification. In addition, the naphthalimide tetrazine Accepted 24th June 2021 system was used for the no-wash imaging of insulin amyloid fibrils in vitro, providing a new method that DOI: 10.1039/d1cb00128k can monitor their growth kinetics and morphology. Since our synthetic approach is simple and modular, these new naphthalimide tetrazines provide a novel scaffold for a range of bioorthogonal tetrazine- rsc.li/rsc-chembio based imaging agents for selective staining and sensing of biomolecules. This article is licensed under a Introduction have attracted much attention due to their ability to quench fluorescence via both through-space Fo¨rster resonance energy Fluorescent probes are a mainstay of molecular imaging, transfer (FRET)9 and through-bond energy transfer (TBET) 10–12 Open Access Article. Published on 05 July 2021. Downloaded 9/23/2021 12:29:10 PM. providing previously inaccessible information about the processes. They have been shown to react rapidly complex chemistry of biomolecules, cells and organisms.1–3 (second-order rate constants up to 106 MÀ1 sÀ1)4 in inverse Recent advances in bioorthogonal chemistry have allowed for electron demand Diels Alder (IEDDA) reactions with a range of the development of fluorogenic probes, for which fluorescence strained dienophiles such as trans-cyclooctenes8 and intensities dramatically increase upon a click reaction with a bicyclononynes.13 The IEDDA reaction of a tetrazine with a 4,5 bioorthogonal partner. These fluorogenic probes have been strained cycloalkyne produces a pyridazine with only N2 as a by- extensively used to image biological structures, revealing their product (Fig. 1A). Fluorescence is restored to the fluorophore as significance during health and disease.6 pyridazines do not quench fluorescence through energy trans- Of the suite of bioorthogonal reactions developed for studies fer and hence the tetrazine-BCN ligation is an excellent strategy of biological processes, the tetrazine ligation has been exten- for fluorogenic labelling.14 sively utilized for fluorogenic probes.7,8 The 1,2,4,5-tetrazines Many tetrazine-containing fluorogenic probes have been synthesized with emission wavelengths spanning the visible and infrared spectrum, commonly employing coumarin,15 a The University of Sydney, School of Chemistry, NSW, 2006, Australia. fluorescein,16 rhodamine,17 cyanine,18 BODIPY12 and other E-mail: [email protected] 19–25 b Australian Research Council Centre of Excellence for Innovations in Peptide and commercial and novel scaffolds. All of these have been Protein Science, The University of Sydney, NSW, 2006, Australia utilized in confocal microscopy, and some for super resolution 26–28 c The University of Sydney, School of Medical Sciences, Faculty of Medicine and imaging. Typically, these reports require the genetic mod- Health, NSW, 2006, Australia ification of a native protein to incorporate a bioorthogonal d The University of Sydney Nano Institute (Sydney Nano), The University of Sydney, reactive group and this method only provides information on NSW, 2006, Australia e CEISAM Lab, CNRS, Universite´ de Nantes, Nantes, France the localization of that macromolecule. The few notable excep- † Electronic supplementary information (ESI) available. See DOI: 10.1039/ tions, where fluorogenic tetrazines have been used for targeted 2+ d1cb00128k or analyte sensing, include: a Mg fluorescent sensor with a © 2021 The Author(s). Published by the Royal Society of Chemistry RSC Chem. Biol. View Article Online Paper RSC Chemical Biology In this work, we describe the efficient synthesis and photo- physical properties of the first series of naphthalimide tetra- zines that can be used for biological imaging. Using the optimized scaffold from these studies, we developed live cell fluorogenic organelle-targeted probes that do not require genetic modification or antibody-based stains. In addition, the naphthalimide tetrazines were used to label insulin amy- loid fibrils in vitro, without washing and without affecting their growth kinetics. Results and discussion Design and synthesis In our previous work with substituted naphthalimides, we identified that derivatives with substituents installed at the 3- and 6-position on the naphthalene core exhibited the best photophysical properties for imaging.32 We chose to conjugate the tetrazine at the 3- and 6-positions with a phenyl ring to ensure TBET quenching.12 FRET quenching is also expected to occur in this molecule as the naphthalimide and tetrazine are in close proximity. As FRET is directional, it was anticipated that the configuration across the phenyl ring would cause Creative Commons Attribution-NonCommercial 3.0 Unported Licence. different degrees of quenching.15 Hence, we investigated mole- cules in which the tetrazine was installed in meta and para Fig. 1 (A) Fluorescent tagging of biomolecules using the tetrazine liga- configurations on the phenyl ring, relative to the naphthali- tion. Tetrazines quench appended fluorophores via FRET and TBET and mide. Four compounds were designed to explore the relative after reaction with a cycloalkyne, form a pyridazine which does not degree of quenching and subsequent fluorescence turn-ons of quench fluorescence. (B) Synthesis of the four desired naphthalimide tetrazines through the coupling of 1a or 1b with 2a or 2b. naphthalimide tetrazines. A convergent synthetic route was envisaged, employing a convergent cross-coupling between bromo-naphthalimides and This article is licensed under a tetrazine for organelle-localized Mg2+ detection;29 a fluorogenic tetrazine-aryl-boronate esters as the final step. 3-Bromo- reaction to quantify endocytosis of antibody conjugates;30 and using naphthalimide (1a) and 6-bromo-naphthalimide (1b) were tetrazines as a phototrigger to activate organelle-targeted stains.31 obtained from anhydride intermediates in moderate yields using previously reported conditions (Scheme S1, ESI†).42 The Open Access Article. Published on 05 July 2021. Downloaded 9/23/2021 12:29:10 PM. We ascribe the lack of development in this area due to the challenge of finding fluorescent moieties which have synthetic handles that tetrazine-aryl-boronate esters were synthesized using condi- can be readily decorated with sensing or targeting groups. tions recently reported by Mao et al. for the thiol-catalyzed 43 The 4-amino-1,8-naphthalimides are a class of fluorophores formation of tetrazines from aryl nitriles. Hence, bromophe- for which tetrazine conjugates for bioimaging applications have nyltetrazines were then prepared from 3-bromobenzonitrile not been reported to date. These fluorophores have great and 4-bromobenzonitrile respectively. Miyaura borylation of potential for bioimaging due to their brightness, large Stokes these bromide intermediates afforded the boronate esters 2a shifts and good photostability.32 In addition, they can be and 2b in good yields (Scheme S1, ESI†). The two boronate readily synthetically modified at the imide, 4-amino-position esters were then coupled to the two bromo-naphthalimides in and 3-, 5- or 6-positions of the naphthalene core.32,33 There are all combinations using standard Suzuki cross-coupling condi- some reports of fluorogenic naphthalimides for biological tions, affording the four desired naphthalimide tetrazines in imaging and protein labelling, with the fluorogenic changes moderate yields (Fig. 1B). arising from click reactions involving azides and alkynes,34 SNAP tags,35 sydnones,36 and oximes.37 However, there are no Photophysical properties reports of fluorogenic 4-amino-naphthalimides incorporating With the four candidates in hand, we first established that tetrazines for biological imaging. To the best of our knowledge, none of the unreacted tetrazine products was significantly the only two naphthalimide tetrazines reported to date were fluorescent. While all compounds showed significantly developed for electrochemical applications and not applied to quenched fluorescence, a weak emission band was observed biological imaging. They were unsuitable for biological applica- around 530 nm in ethanol for all compounds (Table 1). To tion as these reports used a 1,8-naphthalimide that
Load more

Recommended publications
  • Stabilization of Anti-Aromatic and Strained Five-Membered Rings with A
    ARTICLES PUBLISHED ONLINE: 23 JUNE 2013 | DOI: 10.1038/NCHEM.1690 Stabilization of anti-aromatic and strained five-membered rings with a transition metal Congqing Zhu1, Shunhua Li1,MingLuo1, Xiaoxi Zhou1, Yufen Niu1, Minglian Lin2, Jun Zhu1,2*, Zexing Cao1,2,XinLu1,2, Tingbin Wen1, Zhaoxiong Xie1,Paulv.R.Schleyer3 and Haiping Xia1* Anti-aromatic compounds, as well as small cyclic alkynes or carbynes, are particularly challenging synthetic goals. The combination of their destabilizing features hinders attempts to prepare molecules such as pentalyne, an 8p-electron anti- aromatic bicycle with extremely high ring strain. Here we describe the facile synthesis of osmapentalyne derivatives that are thermally viable, despite containing the smallest angles observed so far at a carbyne carbon. The compounds are characterized using X-ray crystallography, and their computed energies and magnetic properties reveal aromatic character. Hence, the incorporation of the osmium centre not only reduces the ring strain of the parent pentalyne, but also converts its Hu¨ckel anti-aromaticity into Craig-type Mo¨bius aromaticity in the metallapentalynes. The concept of aromaticity is thus extended to five-membered rings containing a metal–carbon triple bond. Moreover, these metal–aromatic compounds exhibit unusual optical effects such as near-infrared photoluminescence with particularly large Stokes shifts, long lifetimes and aggregation enhancement. romaticity is a fascinating topic that has long interested Results and discussion both experimentalists and theoreticians because of its ever- Synthesis, characterization and reactivity of osmapentalynes. Aincreasing diversity1–5. The Hu¨ckel aromaticity rule6 applies Treatment of complex 1 (ref. 32) with methyl propiolate to cyclic circuits of 4n þ 2 mobile electrons, but Mo¨bius topologies (HC;CCOOCH3) at room temperature produced osmapentalyne favour 4n delocalized electron counts7–10.
    [Show full text]
  • Cycloalkanes, Cycloalkenes, and Cycloalkynes
    CYCLOALKANES, CYCLOALKENES, AND CYCLOALKYNES any important hydrocarbons, known as cycloalkanes, contain rings of carbon atoms linked together by single bonds. The simple cycloalkanes of formula (CH,), make up a particularly important homologous series in which the chemical properties change in a much more dramatic way with increasing n than do those of the acyclic hydrocarbons CH,(CH,),,-,H. The cyclo- alkanes with small rings (n = 3-6) are of special interest in exhibiting chemical properties intermediate between those of alkanes and alkenes. In this chapter we will show how this behavior can be explained in terms of angle strain and steric hindrance, concepts that have been introduced previously and will be used with increasing frequency as we proceed further. We also discuss the conformations of cycloalkanes, especially cyclo- hexane, in detail because of their importance to the chemistry of many kinds of naturally occurring organic compounds. Some attention also will be paid to polycyclic compounds, substances with more than one ring, and to cyclo- alkenes and cycloalkynes. 12-1 NOMENCLATURE AND PHYSICAL PROPERTIES OF CYCLOALKANES The IUPAC system for naming cycloalkanes and cycloalkenes was presented in some detail in Sections 3-2 and 3-3, and you may wish to review that ma- terial before proceeding further. Additional procedures are required for naming 446 12 Cycloalkanes, Cycloalkenes, and Cycloalkynes Table 12-1 Physical Properties of Alkanes and Cycloalkanes Density, Compounds Bp, "C Mp, "C diO,g ml-' propane cyclopropane butane cyclobutane pentane cyclopentane hexane cyclohexane heptane cycloheptane octane cyclooctane nonane cyclononane "At -40". bUnder pressure. polycyclic compounds, which have rings with common carbons, and these will be discussed later in this chapter.
    [Show full text]
  • Strain-Promoted 1,3-Dipolar Cycloaddition of Cycloalkynes and Organic Azides
    Top Curr Chem (Z) (2016) 374:16 DOI 10.1007/s41061-016-0016-4 REVIEW Strain-Promoted 1,3-Dipolar Cycloaddition of Cycloalkynes and Organic Azides 1 1 Jan Dommerholt • Floris P. J. T. Rutjes • Floris L. van Delft2 Received: 24 November 2015 / Accepted: 17 February 2016 / Published online: 22 March 2016 Ó The Author(s) 2016. This article is published with open access at Springerlink.com Abstract A nearly forgotten reaction discovered more than 60 years ago—the cycloaddition of a cyclic alkyne and an organic azide, leading to an aromatic triazole—enjoys a remarkable popularity. Originally discovered out of pure chemical curiosity, and dusted off early this century as an efficient and clean bio- conjugation tool, the usefulness of cyclooctyne–azide cycloaddition is now adopted in a wide range of fields of chemical science and beyond. Its ease of operation, broad solvent compatibility, 100 % atom efficiency, and the high stability of the resulting triazole product, just to name a few aspects, have catapulted this so-called strain-promoted azide–alkyne cycloaddition (SPAAC) right into the top-shelf of the toolbox of chemical biologists, material scientists, biotechnologists, medicinal chemists, and more. In this chapter, a brief historic overview of cycloalkynes is provided first, along with the main synthetic strategies to prepare cycloalkynes and their chemical reactivities. Core aspects of the strain-promoted reaction of cycloalkynes with azides are covered, as well as tools to achieve further reaction acceleration by means of modulation of cycloalkyne structure, nature of azide, and choice of solvent. Keywords Strain-promoted cycloaddition Á Cyclooctyne Á BCN Á DIBAC Á Azide This article is part of the Topical Collection ‘‘Cycloadditions in Bioorthogonal Chemistry’’; edited by Milan Vrabel, Thomas Carell & Floris P.
    [Show full text]
  • WO 2013/089962 Al 20 June 2013 (20.06.2013) W P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2013/089962 Al 20 June 2013 (20.06.2013) W P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every B01J 31/04 (2006.01) B01J 31/18 (2006.01) kind of national protection available): AE, AG, AL, AM, B01J 31/14 (2006.01) B01J 31/22 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (21) Number: International Application DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US20 12/065285 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 15 November 2012 (15.1 1.2012) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, (25) Filing Language: English RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, (26) Publication Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 13/323,328 12 December 201 1 (12. 12.201 1) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant (for all designated States except US): CHEV¬ GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, RON PHILLIPS CHEMICAL COMPANY LP UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, [US/US]; 10001 Six Pines Drive, The Woodlands, Texas TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 77380 (US).
    [Show full text]
  • Highly Accelerated Inverse Electron-Demand Cycloaddition of Electron-Deficient Azides with Aliphatic Cyclooctynes
    ARTICLE Received 22 Jul 2014 | Accepted 25 Sep 2014 | Published 10 Nov 2014 DOI: 10.1038/ncomms6378 Highly accelerated inverse electron-demand cycloaddition of electron-deficient azides with aliphatic cyclooctynes Jan Dommerholt1, Olivia van Rooijen2, Annika Borrmann1,Ce´lia Fonseca Guerra2, F. Matthias Bickelhaupt1,2 & Floris L. van Delft1 Strain-promoted azide–alkyne cycloaddition (SPAAC) as a conjugation tool has found broad application in material sciences, chemical biology and even in vivo use. However, despite tremendous effort, SPAAC remains fairly slow (0.2–0.5 M À 1 s À 1) and efforts to increase reaction rates by tailoring of cyclooctyne structure have suffered from a poor trade-off between cyclooctyne reactivity and stability. We here wish to report tremendous acceleration of strain-promoted cycloaddition of an aliphatic cyclooctyne (bicyclo[6.1.0]non-4-yne, BCN) with electron-deficient aryl azides, with reaction rate constants reaching 2.0–2.9 M À 1 s À 1. A remarkable difference in rate constants of aliphatic cyclooctynes versus benzoannulated cyclooctynes is noted, enabling a next level of orthogonality by a judicious choice of azide– cyclooctyne combinations, which is inter alia applied in one-pot three-component protein labelling. The pivotal role of azide electronegativity is explained by density-functional theory calculations and electronic-structure analyses, which indicates an inverse electron-demand mechanism is operative with an aliphatic cyclooctyne. 1 Institute for Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands. 2 Department of Theoretical Chemistry and Amsterdam Center for Multiscale Modeling, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
    [Show full text]
  • Rapid Calculation of the Number of Π-Bonds, Σ-Bonds, Single and Triple Bonds in Aliphatic Unsaturated Open Chain and Cycloalkynes
    World Journal of Chemical Education, 2014, Vol. 2, No. 1, 1-3 Available online at http://pubs.sciepub.com/wjce/2/1/1 © Science and Education Publishing DOI:10.12691/wjce-2-1-1 Rapid Calculation of the Number of π-bonds, σ-bonds, Single and Triple Bonds in Aliphatic Unsaturated Open Chain and Cycloalkynes Arijit Das1,*, Suman Adhikari1, Debapriya Pal2, Bijaya Paul3, R. Sanjeev4, V. Jagannadham5 1Department of Chemistry, Govt. Degree College, Dharmanagar, Tripura(N), India 2Department of Science, Netaji Vidyapith Institute, Unakoti, Tripura, India 3Department of Chemistry, Tripura University, Suryamaninagar, Tripura(W), India 4Department of Chemistry, Avanthi Degree and PG College, Hyderabad, India 5Department of Chemistry, Osmania University, Hyderabad, India *Corresponding author: [email protected] Received September 20, 2013; Revised December 15, 2013; Accepted December 30, 2013 Abstract Prediction of number of π-bonds, σ-bonds, single and triple bonds of aliphatic unsaturated open chain and cycloalkynes is a vitally important tool for students of chemistry at undergraduate and graduate level for solving different kinds of problems regarding different chemical reactions. In this manuscript, we try to present a simple and innovative method for easy calculation of number of π-bonds, σ-bonds, single and triple bonds with the help of completely 8 (eight) new formulae. Keywords: open chain and cycloalkynes, π and σ-bond, triple and single bond, number of carbon, hydrogen atoms Cite This Article: Arijit Das, Suman Adhikari, Debapriya Pal, Bijaya Paul, R. Sanjeev, and V. Jagannadham, “Rapid Calculation of the Number of π-bonds, σ-bonds, Single and Triple Bonds in Aliphatic Unsaturated Open Chain and Cycloalkynes.” World Journal of Chemical Education 2, no.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2009/0068738A1 BERTOZZ Et Al
    US 20090068738A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0068738A1 BERTOZZ et al. (43) Pub. Date: Mar. 12, 2009 (54) COMPOSITIONS AND METHODS FOR Related U.S. Application Data MODIFICATION OF BOMOLECULES (63) Continuation-in-part of application No. 1 1/264,463, filed on Oct. 31, 2005. (75) Inventors: CAROLYN RUTH BERTOZZI, (60) Provisional application No. 60/624.202, filed on Nov. BERKELEY, CA (US); 1, 2004. NICHOLAS J. AGARD, BERKELEY, CA (US); Publication Classification JENNIFER A. PRESCHER, (51) Int. Cl. BERKELEY, CA (US): JEREMY CI2N 5/06 (2006.01) MICHAEL BASKIN, C07D 495/04 (2006.01) BERKELEY, CA (US); ELLEN CD7C 65/26 (2006.01) MAYSLETTEN, BERKELEY, CA C7H I/00 (2006.01) (US) (52) U.S. Cl. ...................... 435/375: 548/304.1; 540/480; 562/473; 536/55.3 Correspondence Address: (57) ABSTRACT BOZICEVIC, FIELD & FRANCIS LLP The present invention provides modified cycloalkyne com 1900 UNIVERSITY AVENUE, SUITE 200 pounds; and method of use of Such compounds in modifying EAST PALOALTO, CA 94.303 (US) biomolecules. The present invention features a cycloaddition reaction that can be carried out under physiological condi (73) Assignee: THE REGENTS OF THE tions. In general, the invention involves reacting a modified UNIVERSITY OF cycloalkyne with an azide moiety on a target biomolecule, CALIFORNLA, Oakland, CA (US) generating a covalently modified biomolecule. The selectiv ity of the reaction and its compatibility with aqueous envi ronments provide for its application in Vivo (e.g., on the cell (21) Appl. No.: 12/049,034 Surface or intracellularly) and in vitro (e.g., synthesis of pep tides and other polymers, production of modified (e.g., (22) Filed: Mar.
    [Show full text]
  • IUPAC Nomenclature Rule for Alkyne
    IUPAC nomenclature Rule for Alkyne (1) Select the longest carbon chain containing a triple bond (2) The numbering of the carbon chain is in such a way that the carbon attached to the triple bond should get the lowest possible number (3) The numbering of the triple bond carbon should be mentioned in the nomenclature (4) All other rules of substituents are the same as alkanes and alkenes ethyne 1-propyne 5-methyl-2-hexyne Nomenclature of cycloalkynes: Nomenclature is according to the suffix = cycloalkyne 4-methyl cyclopentyne cyclohexyne 3-methyl cyclobutyne IUPAC nomenclature Rule for Compounds containing both double and triple bonds (1) If the organic compound contains both double and triple bond, then select the longest carbon chain in such a way that the sum of the carbons attached to the double and triple bond should get the lowest possible number. 1-hexene-3-yne 1 + 3 = 4 (Correct numbering - small sum total) 3 + 5 = 8 (Incorrect numbering - large sum total) (2) Nomenclature is always according to the alkene followed by alkyne i.e. Prefix = alkene, Suffix = alkyne (3) If the sum of the carbons attached to double and triple bond is the same (for both LHS to RHS and RHS to LHS), then select the longest carbon chain in such a way that carbon attached to the double bond should get the lowest possible number 1-butene-3-yne 1 + 3 = 4 (Correct numbering - small sum total) 1 + 3 = 4 (Correct numbering - small sum total) (4) Numbering from LHS to RHS is correct because double bond carbon gets the lower possible number .
    [Show full text]
  • Certified by
    Estimation Method for the Thermochemical Properties of Polycyclic Aromatic Molecules by Joanna Yu Bachelor of Science in Engineering, Escola Politcnica-USP, Sao Paulo, Brazil, 2001 Submitted to the Department of Chemical Engineering in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemical Engineering Practice at the MASSACHUSETTS INSTITUTE OF TECHNOLOGY September 2004 © Massachusetts Institute of Technology 2004. All rights reserved. Author. · epartment of Chemical Engineering September 1, 2004 Certifiedbyby ............... .............. ,f.\.. ................................... (U)William H. Green, Jr. Texaco-Mangelsdorf Associate Professor Thesis Supervisor Acceptedby............ ................... ..... Daniel Blankschtein Professor of Chemical Engineering Chairman, Committee for Graduate Students MASSACHUSETTS INSTTUTE OF TECHNOLOGY F SEP 12 2005 _ 11"C4,1~e- LIBRARIES Estimation Method for the Thermochemical Properties of Polycyclic Aromatic Molecules by Joanna Yu Bachel)or of Science in Engineering, Escola Polit6cnica-USP, So Paulo, Brazil, 2001 Submitted to tle Departmenlt of Chemical Engineering on September 1, 2004, in partial fulfillment of the requiremlents for tle degree of Doctor of Philosophy in Chemical Engineering Practice Abstract Polycy( lic aromatic molecules, icluding polycyclic aromatic hydrocarbons (PAHs) have attracted c(onsiderable attention in the Ipast few decades. They are formed dur- ing the incomipliete combustion of hydrocarbon fuels and are precursors of soot. Some PAHs are known carcilnogens, and control of their emissions is an important issue. These nlolecules uarefound in Ilany materials, including coal, fuel oils, lubricants, andl carton )l lack. They are also ilmpi)licatedi tle formation of fullerenes, one of the Ilost. chemi(( ally versatile class of molecules known. Clearly, models that p)rovide predic- tive cap:,ability for their formation and growth are highly d(esiral)le.
    [Show full text]
  • Mechanisms of Metal-Mediated Cyclizations
    Mechanisms of Metal-Mediated Cyclizations by Benjamin Peter Warner Submitted to the Department of Chemistry in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Organic Chemistry at the Massachusetts Institute of Technology February 1995 © Massachusetts Institute of Technology, 1995 All Rights Reserved Signature of Author.., .... ..,. ....................... ................................................................ Department of Chemistry February 1, 1995 Certified by ........................... I....................... Stephen L. Buchwald Thesis Supervisor Accepted by.............................................v..................................................................... Dietmar Seyferth Chair, Departmental Committee on Graduate Students Sciencx- This doctoral thesis has been examined by a committee of the Department of Chemistry as follows: Professor Gregory C. Fu.............................. .... ........................................................... Chair Professor Stephen L. Buchwald .................. ;................... Thesis Supervisor Professor Christopher C. Cummins.................. ................. .. ...............................; 2 Mechanisms of Metal-Mediated Cyclizations by Benjamin Peter Warner Submitted to the Department of Chemistry in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Organic Chemistry at the Massachusetts Institute of Technology Abstract A complex of zirconocene with two rq2-alkynyl ligands is described. This
    [Show full text]
  • Max-Planck-Institut Für Kohlenforschung Report for The
    Max-Planck-Institut für Kohlenforschung Report for the Period of January 2002 – December 2004 Printed May 2005 Max-Planck-Institut für Kohlenforschung Kaiser-Wilhelm-Platz 1 45470 Mülheim an der Ruhr, Germany Tel. +49 208 3 06 1 Fax +49 208 3 06 29 80 http://www.mpi-muelheim.mpg.de Managing Director Professor Dr. Ferdi Schüth Director of the Department of Synthetic Organic Chemistry Professor Dr. Manfred T. Reetz Tel. +49 208 3 06 20 00 Fax +49 208 3 06 29 85 E-mail: [email protected] Director of the Department of Homogeneous Catalysis NN Director of the Department of Heterogeneous Catalysis Professor Dr. Ferdi Schüth Tel. +49 208 3 06 23 73 Fax +49 208 3 06 29 95 E-mail: [email protected] Director of the Department of Organometallic Chemistry Professor Dr. Alois Fürstner Tel. +49 208 3 06 23 42 Fax +49 208 3 06 29 94 E-mail: [email protected] Director of the Department of Theory Professor Dr. Walter Thiel Tel. +49 208 3 06 21 50 Fax +49 208 3 06 29 96 E-mail: [email protected] External Scientific Members of the Max-Planck-Institut für Kohlenforschung Professor Dr. Alois Haas Medonstrasse 17 14532 Kleinmachnow Germany Professor Dr. Jack Halpern University of Chicago Department of Chemistry 5735 South Ellis Avenue Chicago, Illinois 60637 USA Professor Dr. Walter Leitner Lehrstuhl für Technische Chemie und Petrolchemie Institut für Technische und Makromolekulare Chemie Rheinisch-Westfälische Technische Hochschule Aachen Worringer Weg 1 52074 Aachen Germany Member of the Scientific Council of the Max Planck Society, Section of Chemistry, Physics and Technology Professor Dr.
    [Show full text]
  • From an Enediyne Core Biosynthetic Hypothesis to the Hexadehydro-Diels–Alder Reaction
    Spontaneity to Serendipity: From an Enediyne Core Biosynthetic Hypothesis to the Hexadehydro-Diels–Alder Reaction A DISSERTATION SUBMITTED TO THE FACULTY OF THE GRADUATE SCHOOL OF THE UNIVERSITY OF MINNESOTA BY Brian Patrick Woods IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY Thomas R. Hoye, Adviser August 2014 © Brian Patrick Woods 2014 i Acknowledgements While my name is on the first page of this thesis, countless family, friends, and colleagues contributed their knowledge, support, and love to help make this document a reality. First and foremost, I need to thank my family. I owe everything to my parents, Steve and Diane, who were my first teachers and have been and continue to be inspiring examples of how a life of constant learning and exploration never gets old. They instilled in me their value in the benefits of education and the doors it opens for those willing to knock. For both my siblings and I, they always encouraged us to pursue our dreams and desires—from CSI investigator, to Broadway actor, to NASA scientist—and provided us with the guidance and support to reach them. To my sister and brother, Shannon and Tyler, I thank them for their innate ability to keep me grounded and their unwavering confidence in me. To each of them, along with their partners Braxton and Esther, and my nephew Harrison, I thank them for being a constant reminder that there’s nothing more important than family. For their continual love I would also like to thank my extended family of aunts, uncles, and cousins—and more specifically my grandparents Patrick and Virginia Woods.
    [Show full text]